[Note: The full text of this article is available free here. Rheumatoid arthritis is associated with elevated risks of serious infections, lymphomas and fatal cardiovascular events. The drug rituximab is used in combination with methotrexate to control autoimmune damage to RA patients' joints by reducing levels of a specific immune B-cell that attacks them. The therapy initially elevates risk of infection and malignancy somewhat. This long-term tracking study reflected a concern about the possibility that repeated courses of rituximab might further increase these risks. The findings will be of interest to researchers conducting experimental trials of rituximab as a potential treatment for ME/CFS as well.]

Results:
As of September 2010, 3,194 patients had received up to 17 rituximab courses over 9.5 years (11,962 patient-years). Of these, 627 had more than 5 years' follow-up (4,418 patient-years).

A pooled placebo population (n=818) (placebo + methotrexate (MTX)) was also analyzed.

Serious adverse event and infection rates generally remained stable over time and multiple courses.

• The overall serious infection event (SIE) rate was 3.94 per 100 patient-years (3.26 per 100 patient-years in patients observed for more than 5 years) and was comparable with placebo+MTX (3.79 per 100 patient-years).

• Serious opportunistic infections were rare.

• Overall, 22.4% (n=717) of rituximab-treated patients developed low immunoglobulin (Ig)M and 3.5% (n=112) low IgG levels for 4 months or more after 1 or more courses.

• Serious infection event rates were similar before and during/after development of low Ig levels; however, in patients with low IgG, rates were higher than in patients who never developed low IgG.

• Rates of myocardial infarction and stroke were consistent with rates in the general RA population.

• No increased risk of malignancy over time was observed.

Conclusion:

This analysis demonstrates that rituximab remains generally well tolerated over time and multiple courses, with a safety profile consistent with published data and clinical trial experience.

Overall, the findings indicate that there was no evidence of an increased safety risk or increased reporting rates of any types of adverse events with prolonged exposure to rituximab during the 9.5 years of observation.